May 08, 2019 03:22 PM EDT
At present, there are no disease-modifying therapies for the treatment of Parkinson's disease. One potential strategy for treatment, however, is to prevent a-synuclein aggregation. A team of researchers at Osaka University have developed a device that can assess the degree of a-synuclein aggregation in the brain as a first step.
a-Synuclein is a significant component of Lewy bodies, the pathological hallmark of Parkinson's disease, and a-synuclein aggregation in the brain has been connected to disease onset and progression. A therapy that prevents the accumulation of misfolded a-synuclein is, therefore, a promising strategy.
Methods to assess levels of a-synuclein, however, have not been well established. As a result, the efficacy of any such treatment cannot be tested. To address this issue, Osaka University's team of researchers led by Hideki Mochizuki developed the HANdai Amyloid Burst Inducer (HANABI) device which is a fully automated tool that can accurately detect a-synuclein aggregation in cerebrospinal fluid using ultrasonication. The researchers have published their findings in Scientific Reports.
Mochizuki explained that this system has the potential to distinguish patients with Parkinson's disease from controls based on the seeding activity of a-synuclein aggregates in cerebrospinal fluid. It means HANABI device is sensitive enough to have real clinical potential and supports the idea that a-synuclein aggregation is a marker of the disease.
The seeding activity of a-synuclein describes its ability to change healthy a-synuclein protein into abnormal aggregates. The interesting part is that the seeding activity of cerebrospinal fluid evaluated by the HANABI assay was correlated with the uptake of 123I-meta-iodobenzylguanidine, which is a prominent radiological feature of Parkinson's disease; low uptake has been linked to neurodegeneration. Consequently, seeding activity in the cerebrospinal fluid of patients with Parkinson's disease could reflect the progression of Lewy body pathology.
Also, the HANABI device allows for single processing time. It uses ultrasonication to amplify a-synuclein aggregates that are capable of seeding so that they can be measured. Ultrasonication induces pressure variations, transforming sound waves into mechanical energy. This process increases a-synuclein seeds more rapidly than the alternative method of orbital shaking which reduces the time necessary to perform the assay.
Keita Kakuda, the lead author of the study, explained that the team developed HABANI device to overcome limitations of existing methods and process multiple samples simultaneously. He concluded that this method has allowed them to drastically shorten the time to perform the assay from around ten days to only several hours. The authors of the study expect that the HANABI device will be used for clinical diagnosis, severity assessment, and treatment development for Parkinson's disease.
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